This project examines the physiological effects and the underlying biochemical mechanisms of action of delta opioid peptides and a related protein HIT (Hibernation Induction Trigger) in tissue survival. In this fiscal year, we found that in isolated rabbit heart preparation in which hearts were subjected to 18 hrs of global ischemia, DADLE greatly enhances the functional recovery of myocardial functions. This action of DADLE is blocked by the selective delta2 opioid receptor antagonist. We also extend our finding on the tissue protective property of DADLE from the peripheral system to the central nervous system by examining if DADLE might protect against methamphetamine(METH)-induced dopaminergic (DA) neuronal damage in mouse brain. Results indicate that DADLE dose-dependently blocks the METH-induced DA damage. This action of DADLE may involves opioid receptors as opioid antagonist naltrexone partially reverses this action of DADLE. We also found that DADLE is an antioxidative agent in vitro, suggesting that part of the ation of DADLE as a protective agent against METH-induced DA neuronal damage may involve a sequestration of free radicals which are known to play a role in METH neurotoxicity.